Method for hydrogenating pyrazine and derivatives of pyrazine



2,843,589 Patented July 15, 1958 2,843,589 METHOD FOR HYDROGENATING PYRAZINE AND DERIVATIVES F PYRAZINE Joseph J. Scigliano, Midland, Mich., assignor to The Dow Chemical Company, Midland, Mich., a corporation of Delaware N0 Drawing. Application November 18, 1955 Serial No. 547,854 12 Claims. (Cl. 260268) This invention relates to an improved method for hydrogenating pyrazine and alkylpyrazines to the corresponding piperazine products.

It has been proposed by Godchat and Mousseron to hydrogenate 2,5-dimethylpyrazine in the vapor phase over a nickel catalyst at temperatures between about 150 and 160 C. and under atmospheric pressure to obtain 2,5-dimethylpiperazine. See Comptes Reudus, 190, 798-800 (1930). Such a method however, if it is operative at all, does not produce the desired product in quantities greater than mere trace amounts. It could not, for example, be satisfactorily employed for the manufacture of substantial quantities of piperazine products from corresponding pyrazines and pyrazine derivatives.

It is among the principal objects of the present invention therefore, to provide a method which could be employed satisfactorily for hydrogenating pyrazine and alkyl pyrazines to the corresponding .piperazine products in order to convert the starting materials in substantial quantities and with efficient yields to the desired products.

According to the present invention, pyraz-ine and alkylpyrazines may be hydrogenated to piperazine and alkylpiperazines by. subjecting the pyrazine compound to hydrogen in the presence of a suitable hydrogenation catalyst at a hydrogenation-favoring temperature for the catalyst under a pressure of at least about 200 pounds per square inch and advantageously between about 450 and 600 pounds per square inch. Various hydrogenation catalysts may be satisfactorily employed. Advantageously a hy drogenation catalyst selected from the group consisting of Raney nickel, Raney cobalt, supported reduced nickel, supported rhodium, supported palladium, platinum oxide and the like may be utilized. Piperazine products in substantial quantity may be manufactured with high conversions and yields of the starting pyrazine compounds according to the method of the present invention. Conversions of the pyrazine compound in the neighborhood of 80 to 95 percent and higher may be commonly experienced by this method. When certain alkylated pyrazines are hydrogenated, particularly the 2,5-dialkylpyrazines, the piperazine product may be found to contain substantial portions of the trans isomer thereof. This is particularly the case when 2,5-dimethylpiperazine is produced. Frequently a major proportion of the product may be found to be the trans isomer of 2,S-dimethylpiperazine. Often an amount of trans-2,S-dimethylpiperazine in excess of 80 percent by Weight may be found contained in the product. The yield of trans isomer is facilitated by the employment of nickel hydrogenation catalysts. Supported reduced nickel catalysts, particularly when the support is comprised l of activated alumina, may advantageously be utilized for this purpose.

The pyrazine compounds besides pyrazine which may be employed in the practice of the present invention are alkylpyrazines containing from 1 to 4 carbon atoms in the substituent alkyl groups. Advantageously pyrazine compounds having the general formula:

wherein R is selected from the group consisting of the mentioned alkyl radicals or hydrogen, may be hydrogenated to corresponding piperazine products having the formula:

RH H2 wherein R is the alkyl radical or hydrogen. 2,5-dimethylpyrazine may be hydrogenated with special benefits according to the method of the invention, especially when it is desired to obtain large proportions of the transisomer in the piperazine product.

Suitable operating temperatures for the practice of the hydrogenation method of the present invention will vary with the particular hydrogenation catalyst which is employed. It is usually best conducted within the optimum hydrogenation-favoring temperature range of the catalyst. Thus, various nickel catalysts ordinarily per-form best in the method of the present invention when the hydrogenation is conducted at a temperature between about 200 and 225 C. Raney cobalt, being a somewhat more active catalyst than nickel, will operate well in a slightly lower temperature range. Supported palladium may be employed at temperatures between about and C. while supported rhodium functions satisfactorily at a temperature in the neighborhood of 125-l30 C. Platinum catalysts, being still more active, are useful at even lower operating temperatures.

Usually an amount of catalyst less than about-5 percent by weight of the pyrazine compounds being hydrogenated may be satisfactorily employed. However, this may also vary with the specific activity of given catalysts in the method of the invention and the rapidity with which it is desired to effect a particular conversion. Thus, amounts of palladium catalysts of less than about 1 percent by weight and of rhodium catalysts of less than about 2 percent by weight may frequently render efiicient batch conversions in short periods of time whereas such a catalyst as Raney nickel may be required in an amount as great as about 12 percent by weight of the charge in order to elfect a satisfactory conversion Within practicable time limits.

It is advantageous to select the catalyst on a basis which includes such economical considerations as initial cost, catalyst longevity and resistance to becoming poisoned, operating temperatures .and the adaptability of the'catalyst to being readily reactivated for reuse. Supported reduced nickel catalysts on inert supporting materials which have no deleterious influence on the catalyst metal and which are not harmfully aifected by temperature changes may be employed. Such catalysts as nickel on pumice, or on activated aliunina, silica, diatomaceous earth, fire.- brick and the like are highly attractive in the mentioned particulars for employment in the method of the present invention.

It is convenient to practice the invention with the pyrazine compound to be hydrogenated in the liquid phase and converted by batch-Wise techniques using pressure bombs and like apparatus for the hydrogenation. By such a procedure, satisfactorily high conversions of the pyrazine product can be commonly attained within reaction times of less than 2 hours and frequently in less than an hour. However, if it is preferred, the method can be conducted on a continuous basis by passing the reactant materials through a reaction chamber which contains the hydrogenation catalyst. It is beneficial for purposes of continuous reaction to utilize a vapor phase technique in which a stream of hydrogen, saturated with the vaporized pyrazine compound, is passed over the hydrogenation catalyst in the reaction chamber. Such U a technique is also advantageously employed for the preparation of 2,5-dialkylpiperazines in that it provides a desirable method for the manufacture of product which may consist substantially completely of the trans isomer indicated in the following table, showed very little hydrogenation to have occurred. To the contrary, the operating conditions tended to favor the occurrence of dehydrogenation. This was proven by incorporating about 7 percent of 2,5-dialkylpiperazine. of 2,5-dimethylpiperazine with the vaporized dimethyl- Greater conversions may be obtained by employing pyrazine (DMPy). The weight percentages of obtained quantities of hydrogen which are in excess of stoichioproduct in the table, are based on the amount of 2,5-d1- metric requirements. Particularly when batch techniques methylpiperazine condensate actually recovered from the are employed, it is advantageous to employ at least about reaction. It is significant to note run 8 was performed a 50 percent excess of hydrogen. at superatmospheric pressure (which was not suggested The piperazine products may be recovered from the by Godchat ct al.) and that in most of the runs, dehydroreaction mass according to various techniques which are genation occurred. In all of the runs the catalyst bed apparent to those skilled in the art. For example solvent consisted of 35 percent reduced nickel on activated extraction, filtration, distillation and crystallization alumina.

Catalyst Abs. P., Feed M01 ratio, Wt. per Run Temp, Atmos- DMPy, parts H2 cent DMP Remarks 0. pheres gmsJhr. to one part inproduct DMPy 155 1 116.4 4.76 5.00 Yellow condensate,

no solid. 155 1 116.4 7.32 5.00 Light yellow conden- S 8. 155 1 67.0 7.32 5.00 Colorless condensate. 155 1 116. 4 11.8 5. 84 155 1 90. 0 11.8 5. so 155 1 116. 4 14. 0 6. 7 155 1 22.4 14.0 7.20 No solid. s 155 2 11.0 29 9. 85 Little solid. 9 160-165 1 11.0 42.5 4. 50 No solid.

7 percent by wt. DMP included in feed. Condncted under superatmospherlc pressure. DMP is dimethylpiperazine.

DMPy is dimethylpyraziue.

procedures may be employed in any desired or necessary manner in order to obtain the product in a required pure condition.

In order to further illustrate the invention, but without being restricted thereto, the following examples are given wherein, unless otherwise indicated, all parts and per centages are to be taken by weight.

Example I About 109.5 grams of 2,5-dimethylpyrazine and 14 grams of a supported reduced nickel catalyst which contained about percent of nickel on diatomaceous earth (Super Cel) were charged to a bomb which was adapted to receive hydrogen under pressure and was equipped with an efiicient rocking mechanism. Hydrogen, under an initial pressure of about 408 pounds per square inch, gauge (p. s. i. g.) was admitted to the bomb. The reastion mass was maintained at a temperature of about 210 C. and was continuously rocked for about 3 hours. At the end of this period the drop in pressure in the bomb due to the uptake of hydrogen indicated an overall conversion of about 84.4 percent of theory. The reaction mass was cooled rapidly to produce a solid precipitate which was taken up in hot acetone. The hot acetone solution was filtered and cooled to yield about 29 grams of trans-2,S-dimethylpiperazihe. Distillation of the filtrate produced an additional 69 grams of material which was recrystallized from acetone to render about 56.2 grams of trans-2,5-dimethylpiperazine. Analysis of the filtrate indicated that it contained about 6.3 grams of the cis isomer of 2,5-dimethylpiperazine which represented about 12 percent of the combined product. The overall yield of 2,5-dimethylpiperazine was about 84 percent of theory. The product contained about 13.5 parts by weight of the trans isomer of 2,5-dimethylpiperazine to each part by weight of the cis isomer thereof.

By way of contrast, to illustrate the inadequacy of the proposed methodof Godchat et al., vaporized 2,5-dimethylpyrazine was passed with varying proportions of hydrogen over a supported activated nickel catalyst at a temperature of about 155 C. to 165 C. under pressures of about 1 and 2 atmospheres. The results, as

In addition, it is apparent that, at best, only very little of the trans isomer is produced in the method of Godchat et al. notwithstanding the report made in the reference that substantially all of the hydrogenated product was the trans isomer of 2,5 -dimethylpiperazine.

Example II Following the general procedure of Example I, 2,5-dimethylpyrazine was hydrogenated to 2,5-dimethylpiperazine at a temperature of about 225 C. and under a pressure of about 500 p. s. i. g. using several 35 percent nickel catalysts supported on activated alumina. Conversions of from about 78 to percent of the dimethylpyrazine were obtained within a reaction period of about 1% hours.

In a similar manner and within the same reaction period, a conversion of about 65 percent was obtained with Raney nickel employed in an amount of about 11.75 percent of the charge of 2,5-dimethylpyrazine. Nickel reduced from its nitrate and supported on firebrick (Sil- O-Cel) gave a conversion of about 50 percent under the same conditions. Nickel on firebrick reduced from nickel hydroxide provided about a 38 percent conversion. A catalyst consisting of 35 percent of reduced nickel on Super-Cel employed so that about 4.3 percent of nickel was included in the reaction mass gave an almost complete conversion of about 99.5 percent of the dimethylpyrazine in the 1% hour reaction period. A catalyst consisting of 50 percent reduced nickel on silica produced a 63 percent conversion whereas a catalyst consisting of about 60 percent nickel on activated alumina in which the nickel was not entirely reduced gave less than a 20 percent conversion in this period. Five percent palladium on charcoal at a reaction temperature of about C. converted 99.5 percent of the dimethylpyrazine within 1% hours even though only about 0.66 percent of palladium was present in the charge. In all cases, the converted product represented at least about an 80 percent yield of the trans isomer of 2,5-dimethylpiperazine.

dimethylpyrazine was hydrogenated nsing a catalyst consisting of percent rhodium on charcoal in an amount sufficient to include about 1.6 percent of rhodium in the charge. The reaction temperature was maintained in the neighborhood of 125l30 C. under a pressure of about 500 p. s. i. g. When pure dimethylpyrazine was charged, a complete 100 percent conversion was observed within a minute period. The yield of the trans isomer of 2,5 dimethylpiperazine in the product, however, was only about 36 percent. When two successive batches of dimethylpyrazine were charged as 40 percent aqueous solutions and each was hydrogenated under the same conditions, conversions of 89.5 and 88 percent were obtained in 1% hours even though the same catalyst was reused with the second batch. The hydrogenations in aqueous solution rendered products which represented 52 and 54 percent yields of the trans isomer.

Example IV In a series of six runs, 2,S-dimethylpyrazine was vaporized at temperatures between about 195 and 215 C. and

carried in a stream of hydrogen under a pressure of about 580 p. s. i. g. through a twenty-five inch tower having a one-inch internal diameter which was packed with pellets of 35 percent reduced nickel supported on activated alumina. The catalyst was maintained at a temperature in the neighborhood of about 215-220 C. The following table illustrates the hydrogenation results which were obtained when different rates of feeding the dimethylpyrazine were employed. The freezing point of trans-2,5-dimethylpyrazine is about 116 C.

When the procedures of the foregoing examples are repeated to hydrogenate pyrazine to piperazine and 2,5-

diethylpyrazine to 2,5-diethylpiperazine, similar excellent conversion results may be obtained.

Since certain changes and modifications can readily be entered into in the practice of the present invention without substantially departing from its intended spirit and scope, it is to be understood that all of the foregoing description interpreted as being merely illustrative of the invention and not limiting or restrictive thereof excepting as it is set forth and defined in the appended claims.

What is claimed is:

1. Method for hydrogenating a compound selected from the group consisting of pyrazine, :alkylpyrazines in which each alkyl substituent contains not more than 4 carbon atoms, and mixtures thereof to corresponding piperazine products which consists of subjecting the pyrazine compound to hydrogen in the presence of a hydrogenation catalyst selected from the group consisting of Raney nickel; supported reduced nickel; supported rhodium; and supported palladium at a hydrogenation-favoring temperature for the catalyst, said temperature being between about 125 and 225 C., and under a pressure between about 200 and 600 pounds per square inch.

2. Method for hydrogenating a compound selected from the group consisting of pyrazine, alkylpyrazines in which each alkyl substituent contains not more than 4 carbon atoms, and mixtures thereof to corresponding piperazine products which consists of subjecting the pyrazine compound to hydrogen in the presence of a hydrogenation catalyst selected from the group consisting of Raney nickel; supported reduced nickel; supported rhodium; and supported palladium at a hydrogenation-favoring temperature for the catalyst, said temperature being between about and 225 C., and under a pressure of between about 450 and 600 pounds per square inch.

3. The method of claim 2 wherein the catalyst is a supported reduced nickel catalyst and the temperature is between about 200 and 225 C.

4. The method of claim 3 wherein the reduced nickel catalyst is supported on activated alumina.

5. The method of claim 2 wherein the catalyst is a supported rhodium catalyst and the temperature is between about 125 and C.

6. The method of claim 2 wherein the catalyst is a supported palladium catalyst and the temperature is between about and C.

7. Method for hydrogenating a compound selected from the group consisting of pyrazine, alkylpyrazines in which each alkyl substituent contains not more than 4 carbon atoms, and mixtures thereof to corresponding piperazine products which consists of passing a stream of the pyrazine compound and hydrogen through a bed of a hydrogenation catalyst selected from the group consisting of Raney nickel; supported reduced nickel; supported rhodium; and supported palladium at a hydrogenation-favoring temperature for the catalyst, said temperature being between about 125 and 225 C., and under a pressure between about 450 and 600 pounds per square inch.

8. Method for hydrogenating a compound selected from the group consisting of pyrazine, alkylpyrazines in which each alkyl substituent contains not more than 4- carbon atoms, and mixtures thereof to corresponding piperazine products which consists of passing a stream of hydrogen saturated with the vaporized pyrazine compound through a bed of a reduced nickel catalyst supported on activated alumina at a temperature between about 200 and 225 C. and under a pressure between about 450 and 600 pounds per square inch.

9. Method for hydrogenating 2,5-dimethylpyrazine to obtain 2,5-dimethylpiperazine as a product containing a major proportion of the trans-isomer thereof which c0nsists of subjecting the 2,5-dimethylpyrazine to hydrogen in the presence of a nickel hydrogenation catalyst at a temperature between about 200 and 225 C. and under a pressure between about 450 and 600 pounds per square inch.

10. The method of claim 9 wherein the 2,5-dimethyl piperazine product contains at least about 80 percent by weight of the trans isomer thereof.

11. Method for hydrogenating 2,5-dimethylpyrazine to obtain 2,5-dimethylpiperazine as a product containing at least about 80 percent by weight of the trans isomer thereof which consists of passing a. stream of hydrogen saturated with vaporized 2,5-dimethylpyrazine through a bed of a reduced nickel catalyst supported on activated alumina at a temperature between about 200 and 225 C. and under a pressure between about 450 and 600 pounds per square inch.

12. The method of claim 11 wherein the 2,5-dimethylpiperazine product is comprised substantially completely of the trans isomer thereof.

References Cited in the file of this patent UNITED STATES PATENTS 1,975,843 Gubelmann et a1. Oct. 9, 1934 OTHER REFERENCES Godc-hat et a1.: Bull. Soc. Chim., 51, 349-360 (1932). Armstrong: Trans. Inst. Chem. Engrs. (London), 9, 139-157 (1931). 

1. METHOD FOR HYDROGENATING A COMPOUND SELECTED FROM THE GROUP CONSISTING OF PYRAZINE, ALKYLPYRAZINES IN WHICH EACH ALKYL SUBSTITUENT CONTAINS NOT MORE THAN 4 CARBON ATOMS, AND MIXTURES THEREOF TO CORRESPONDING PIPERAZINE PRODUCTS WHICH CONSISTS OF SUBJECTING THE PYRAZINE COMPOUND TO HYDROGEN IN THE PRESENCE OF A HYDROGENERATION CATALYST SELECTED FROM THE GROUP CONSISTING OF RANEY NICKEL, SUPPORTED REDUCED NICKEL, SUPPORTED RHODIUM, AND USPPORTED PALLADIUM AT A HYDROGENATION-FAVORING TEMPERATURE FOR THE CATALYST, SAID TEMPERATURE BEING BETWEEN ABOUT 125 AND 225*C., AND UNDER A PRESSURE BETWEEN ABOUT 200 AND 600 POUNDS PER SQUARE INCH. 